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Novel mutations in stem cells of young donors can be passed to recipients

20 January 2020
Appeared in BioNews 1031

A new study suggests that rare harmful mutations in young healthy donors' stem cells can be passed on to recipients of stem cell transplants, potentially leading to health problems.

Stem cell transplants can be used to treat some blood disorders and cancers, such as acute myeloid leukaemia (AML), but can also have life-threatening complications such as cardiovascular problems and graft-versus-host disease (GvHD), where new immune cells from the donor attacks the patient's healthy cells.

'There have been suspicions that genetic errors in donor stem cells may be causing problems in cancer patients, but until now we didn't have a way to identify them because they are so rare,' said Dr Todd E Druley, Associate Professor of Paediatrics, Haematology and Oncology at Washington University School of Medicine, St Louis. 'This study raises concerns that even young, healthy donors' blood stem cells may have harmful mutations and provides strong evidence that we need to explore the potential effects of these mutations further.'
 
Researchers analysed samples from patients with AML and their stem cell donors looking at 80 specific genes. The small pilot study identified at least one harmful genetic mutation in 11 of the 25 donors using an advanced sequencing technique. The donors ranged from 20 to 58 years old, with a median age of 26. Researchers later detected the harmful mutations present in donors within the recipients.

These extremely rare, harmful genetic mutations that are present in donors' stem cells do not cause any health problems to the donors, however, they may be passed on to the patients receiving stem cell transplants. Intense chemo- and radiation therapy is required prior to stem cell transplants and the immunosuppression given after the transplant unfortunately allows the rare mutation containing cells the opportunity to replicate quickly, which potentially can create health problems for the patients who receive them.

Co-author, Dr Sima T Bhatt, Assistant Professor of Paediatrics, Haematology and Oncology also at Washington University, said 'Transplant physicians tend to seek younger donors because we assume this will lead to fewer complications. But we now see evidence that even young and healthy donors can have mutations that will have consequences for our patients. We need to understand what those consequences are if we are to find ways to modify them.'

The clinical implications of the findings need to be further studied. Dr Bhatt added: 'Now that we've also linked these mutations to GvHD and cardiovascular problems, we have a larger study planned that we hope will answer some of the questions posed by this one.'

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